DNA ploidy and PTEN as biomarkers for predicting aggressive disease in prostate cancer patients under active surveillance.

BACKGROUND: Current risk stratification tools for prostate cancer patients under active surveillance (AS) may inadequately identify those needing treatment. We investigated DNA ploidy and PTEN as potential biomarkers to predict aggressive disease in AS patients. METHODS: We assessed DNA ploidy by image cytometry and PTEN protein expression by immunohistochemistry in 3197 tumour-containing tissue blocks from 558 patients followed in AS at a Norwegian local hospital. The primary endpoint was treatment, with treatment failure (biochemical recurrence or initiation of salvage therapy) as the secondary endpoint. RESULTS: The combined DNA ploidy and PTEN (DPP) status at diagnosis was associated with treatment-free survival in univariable- and multivariable analysis, with a HR for DPP-aberrant vs. DPP-normal tumours of 2.12 (p < 0.0001) and 1.94 (p < 0.0001), respectively. Integration of DNA ploidy and PTEN status with the Cancer of the Prostate Risk Assessment (CAPRA) score improved risk stratification (c-index difference = 0.025; p = 0.0033). Among the treated patients, those with DPP-aberrant tumours exhibited a significantly higher likelihood of treatment failure (HR 2.01; p = 0.027). CONCLUSIONS: DNA ploidy and PTEN could serve as additional biomarkers to identify AS patients at increased risk of developing aggressive disease, enabling earlier intervention for nearly 50% of the patients that will eventually receive treatment with current protocol.

PTEN and DNA Ploidy Status by Machine Learning in Prostate Cancer.

Machine learning (ML) is expected to improve biomarker assessment. Using convolution neural networks, we developed a fully-automated method for assessing PTEN protein status in immunohistochemically-stained slides using a radical prostatectomy (RP) cohort (n = 253). It was validated according to a predefined protocol in an independent RP cohort (n = 259), alone and by measuring its prognostic value in combination with DNA ploidy status determined by ML-based image cytometry. In the primary analysis, automatically assessed dichotomized PTEN status was associated with time to biochemical recurrence (TTBCR) (hazard ratio (HR) = 3.32, 95% CI 2.05 to 5.38). Patients with both non-diploid tumors and PTEN-low had an HR of 4.63 (95% CI 2.50 to 8.57), while patients with one of these characteristics had an HR of 1.94 (95% CI 1.15 to 3.30), compared to patients with diploid tumors and PTEN-high, in univariable analysis of TTBCR in the validation cohort. Automatic PTEN scoring was strongly predictive of the PTEN status assessed by human experts (area under the curve 0.987 (95% CI 0.968 to 0.994)). This suggests that PTEN status can be accurately assessed using ML, and that the combined marker of automatically assessed PTEN and DNA ploidy status may provide an objective supplement to the existing risk stratification factors in prostate cancer.

Decreasing waiting time for treatment before and during implementation of cancer patient pathways in Norway.

BACKGROUND: In 2015, Norway implemented cancer patient pathways to reduce waiting times for treatment. The aims of this paper were to describe patterns in waiting time and their association with patient characteristics for colorectal, lung, breast and prostate cancers. METHODS: National, population-based data from 2007 to 2016 were used. A multivariable quantile regression examined the association between treatment period, age, stage, sex, place of residence, and median waiting times. RESULTS: Reduction in median waiting times for radiotherapy among colorectal, lung and prostate cancer patients ranged from 14 to 50 days. Median waiting time for surgery remained approximately 21 days for both colorectal and breast cancers, while it decreased by 7 and 36 days for lung and prostate cancers, respectively. The proportion of lung and prostate cancer patients with metastatic disease at the time of diagnosis decreased, while the proportion of colorectal patients with localised disease and patients with stage I breast cancer increased (p < 0.001). After adjusting for case-mix, a patient's place of residence was significantly associated with waiting time for treatment (p < 0.001), however, differences in waiting time to treatment decreased over the study period. CONCLUSIONS: Between 2007 and 2016, Norway experienced improved stage distributions and consistently decreasing waiting times for treatment. While these improvements occurred gradually, no significant change was observed from the time of cancer patient pathway implementation.

Perioperative management of radical cystectomy in the Nordic countries.

Objective: Radical cystectomy is performed in all of the Nordic countries, but the current practice patterns remain unclear. This study explored current perioperative care and adherence to the Early Recovery After Cystectomy (ERAC) protocol and EAU guidelines by cystectomy surgeons in the Nordic countries. Materials and methods: The study was performed as a survey including 47 centers performing cystectomies in Norway, Sweden, Finland, Iceland and Denmark. The survey addressed surgical volume, complications, preoperative imaging, use of chemotherapy, multidisciplinary conferences and current practice for perioperative and postoperative care. The survey was dispersed electronically and data was collected between November 2016 and October 2017. Results: The response rate was 55%, with a 78% completion rate of the 58 main questions. Most centers performed 10-50 cystectomies annually. Of responding centers, 96% had preoperative multidisciplinary conferences. Bowel preparation was avoided in 95% of centers and 92% did not use nasogastric tubes. All centers offered neoadjuvant chemotherapy, prescribed prophylactic antibiotics, used urinary drainage and did in-department follow-up. None of the responders waited for proof of bowel function before restarting oral diet and 96% had a standard plan for early mobilization. Conclusion: This study found a high degree of implementation of ERAC and EAU guidelines and similar practice patterns regarding perioperative management of Radical cystectomy among Nordic countries.

Progress towards a Nordic standard for the investigation of hematuria: 2019.

Objective: To describe the management of patients with hematuria in the Nordic countries in relation to bladder cancer epidemiology, especially in the context of introducing fast track pathways with the aim of proposing a common guideline. Materials and methods: Epidemiological data on bladder cancer from each country, and the combined cancer registry, Nordcan, were analyzed. The evolution of the different national recommendations and the introduction of fast track pathways were assessed. Patients' demographics, type of hematuria and cancer detection rates were analysed if available. Results: The crude incidence of bladder cancer has increased substantially since the 1960s, while the age standardized incidence has been stable during recent decades. The relative survival has increased in all countries, while the mortality has been stable. For those with microscopic hematuria there has been a clear trend towards less rigorous investigations. In the fast track pathways, introduced in three of five countries, about one in five patients with macroscopic hematuria had a cancer diagnosis. Data show that time to diagnosis has been reduced. Conclusions: The number of patients with bladder cancer is increasing in the Nordic region. The introduction of fast track pathways has been important in improving the management of patients with suspicion of the disease. Our recommendation is to focus on macroscopic hematuria in the fast track pathways. Microhematuria without any symptoms should not be an indication for cystoscopy. However, urinary tract symptoms accompanied by microhematuria can still be investigated according to respective guidelines but not necessarily within fast track pathways.